Propionic Acid → N-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)propionamide

HRID 1053238Notes

Reaction equation

HRID 1053238 reaction equation
[C:1]([OH:5])(=O)[CH2:2][CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:30][C:31]1[CH:32]=[C:33]([NH:37][C:38]2[CH:43]=[C:42]([NH:44][C:45]3[CH:50]=[CH:49][C:48]([O:51][C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)=[CH:47][CH:46]=3)[N:41]=[CH:40][N:39]=2)[CH:34]=[CH:35][CH:36]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[O:51]([C:48]1[CH:47]=[CH:46][C:45]([NH:44][C:42]2[N:41]=[CH:40][N:39]=[C:38]([NH:37][C:33]3[CH:32]=[C:31]([NH:30][C:1](=[O:5])[CH2:2][CH3:3])[CH:36]=[CH:35][CH:34]=3)[CH:43]=2)=[CH:50][CH:49]=1)[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1

Participants

6

Reactant 4

HCID 1032Propionic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577082883-[6-(4-Phenoxyphenylamino)-pyrimidin-4-ylamino]phenylamine

Product 1

HCID 57708254N-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)propionamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of propionic acid (12 mg, 0.1 mmol) in DMF (0.6 mL) was added HATU (92 mg, 0.2 mmol) and the reaction mixture was stirred at room temperature for 30 min. To it was added N4-(3-aminophenyl)-N6-(4-phenoxyphenyl)pyrimidine-4,6-diamine (60 mg, 0.1 mmol) followed by DIPEA (41 mg, 0.3 mmol) and the reaction mixture was stirred at this temperature for 16 h. It was concentrated under reduced pressure. The residue was diluted with CH2Cl2 (5 mL) and was washed with NaHCO3 solution (2 mL), water (2 mL), and brine (2 mL). Drying over Na2SO4 followed by concentration under reduced pressure offered a residue that was purified by column chromatography (SiO2, 230-400, chloroform/methanol: 9/1) to give N-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)propionamide (IR-10) as a brown solid. 1H NMR (DMSO-d6) δ ppm: 1.06 (t, J=7.56 Hz, 3H), 2.30 (q, J=7.48 Hz, 2H), 6.13 (s, 1H), 6.94-6.99 (m, 4H), 7.08 (t, J=7.36 Hz, 1H), 7.16-7.24 (m, 3H), 7.36 (t, J=7.44 Hz, 2H), 7.54 (d, J=8.88 Hz, 2H), 7.81 (s, 1H), 8.23 (s, 1H), 9.12 (s, 2H), 9.81 (s, 1H); LCMS: m/e 426.3 (M+1).

Workup

  1. stirringthe reaction mixture was stirred at this temperature for 16 h
  2. concentrationIt was concentrated under reduced pressure
  3. additionThe residue was diluted with CH2Cl2 (5 mL)
  4. washwas washed with NaHCO3 solution (2 mL), water (2 mL), and brine (2 mL)
  5. dry with materialDrying over Na2SO4
  6. concentrationfollowed by concentration under reduced pressure
  7. customwas purified by column chromatography (SiO2, 230-400, chloroform/methanol: 9/1)

Sources & evidence

ORD record
ord-83bfdafbdd744e8890566cac9e16857d
Source dataset
uspto-grants-2016_07
Patent number
US09393246B2

Reaction notes

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